title: Seasonal H3N2 influenza A virus fails to enhance Staphylococcus aureus co-infection in a non-human primate respiratory tract infection model.
abstract: Staphylococcus aureus community-acquired pneumonia is often associated with influenza or an influenza-like syndrome. Morbidity and mortality due to methicillin-resistant S. aureus (MRSA) or influenza and pneumonia, which includes bacterial co-infection, are among the top causes of death by infectious diseases in the United States. We developed a non-lethal influenza A virus (IAV) (H3N2)/S. aureus co-infection model in cynomolgus macaques (Macaca fascicularis) to test the hypothesis that seasonal IAV infection predisposes non-human primates to severe S. aureus pneumonia. Infection and disease progression were monitored by clinical assessment of animal health; analysis of blood chemistry, nasal swabs, and X-rays; and gross pathology and histopathology of lungs from infected animals. Seasonal IAV infection in healthy cynomolgus macaques caused mild pneumonia, but unexpectedly, did not predispose these animals to subsequent severe infection with the community-associated MRSA clone USA300. We conclude that in our co-infection model, seasonal IAV infection alone is not sufficient to promote severe S. aureus pneumonia in otherwise healthy non-human primates. The implication of these findings is that comorbidity factors in addition to IAV infection are required to predispose individuals to secondary S. aureus pneumonia.
authors.affiliation: Laboratory of Human Bacterial Pathogenesis; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kobayashi
authors.affiliation: Center for Molecular and Translational Human Infectious Disease Research; The Methodist Hospital Research Institute; Houston, TX USA; Department of Pathology and Genomic Medicine; The Methodist Hospital; Houston, TX USA.
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Olsen
authors.affiliation: Veterinary Branch; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: LaCasse
authors.affiliation: Laboratory of Virology; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: David
authors.initials: D
authors.lastname: Safronetz
authors.affiliation: Center for Molecular and Translational Human Infectious Disease Research; The Methodist Hospital Research Institute; Houston, TX USA; Department of Medicine; The Methodist Hospital; Houston, TX USA.
authors.forename: Madiha
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Laboratory of Human Bacterial Pathogenesis; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Adeline R
authors.initials: AR
authors.lastname: Porter
authors.affiliation: Laboratory of Human Bacterial Pathogenesis; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Braughton
authors.affiliation: Office of Operations Management; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Friederike
authors.initials: F
authors.lastname: Feldmann
authors.affiliation: Laboratory of Virology; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Dawn R
authors.initials: DR
authors.lastname: Clifton
authors.affiliation: Laboratory of Infectious Diseases; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, MD USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Kash
authors.affiliation: Veterinary Branch; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Bailey
authors.affiliation: Veterinary Branch; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Gardner
authors.affiliation: Laboratory of Human Bacterial Pathogenesis; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Otto
authors.affiliation: Veterinary Branch; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Brining
authors.affiliation: Public Health Research Institute; University of Medicine and Dentistry of New Jersey; Newark, NJ USA.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.affiliation: Laboratory of Infectious Diseases; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Bethesda, MD USA.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Taubenberger
authors.affiliation: Veterinary Branch; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parnell
authors.affiliation: Laboratory of Virology; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Heinz
authors.initials: H
authors.lastname: Feldmann
authors.affiliation: Center for Molecular and Translational Human Infectious Disease Research; The Methodist Hospital Research Institute; Houston, TX USA; Department of Pathology and Genomic Medicine; The Methodist Hospital; Houston, TX USA.
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
authors.affiliation: Laboratory of Human Bacterial Pathogenesis; Rocky Mountain Laboratories; National Institute of Allergy and Infectious Diseases; National Institutes of Health; Hamilton, MT USA.
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
mesh_terms: D000818:Animals; D060085:Coinfection / Q000382:microbiology* / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000254:growth & development*; D008168:Lung / Q000473:pathology; D008252:Macaca fascicularis; D008297:Male; D056265:Microbial Interactions; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000473:pathology / Q000821:virology; D011023:Pneumonia, Staphylococcal / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D013211:Staphylococcus aureus / Q000254:growth & development*
keywords: MRSA; Staphylococcus aureus; USA300; coinfection; influenza a virus; pneumonia